Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogenesis by controlling its release
Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogenesis by controlling its release
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DOI：
10.1002/jbm.a.10061
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发表时间：
2003-10-01
影响因子：
4.9
通讯作者：
Suzuki, Y
中科院分区：
文献类型：
--
作者：
Chinen, N;Tanihara, M;Suzuki, Y
藻酸盐是一种酸性多糖，类似于糖胺聚糖，是用作人工基质的候选物。我们开发了一种新型的与肝素交联的藻酸盐凝胶片（H/A凝胶片），并发现其具有释放具有生物活性的碱性成纤维细胞生长因子（碱性成纤维细胞生长因子）（肝素结合生长因子（HBGFs）的代表成员）的特性，体外约1个月，并在体内诱导血管生成。在本研究中，H/A凝胶片被机械破碎，以产生易于注射的50- 200-μ m的凝胶微粒（H/A凝胶颗粒），其性质进行了分析。H/A凝胶颗粒累积释放的bFGF是H/A凝胶片的2.8倍，尽管两者都具有相同量的bFGF吸附到它们的凝胶上。此外，bFGF吸附的H/A凝胶颗粒释放了大量的bFGF，其刺激人脐静脉内皮细胞培养物中的细胞生长长达5周。皮下注射bFGF吸附的H/A凝胶颗粒诱导凝胶周围组织中形成许多微血管。这些结果表明，H/A凝胶颗粒不仅通过防止蛋白水解或变性的发生来稳定bFGF，而且还调节其从凝胶中的释放。由于H/A凝胶颗粒可以容易地注射到靶组织中，因此这种人工基质可以用于局部递送HBGFs以治疗缺血性动脉疾病，以及用于再生或构建组织。(C)2003 Wiley Periodicals，Inc.
Alginate is an acidic polysaccharide like the glycosaminoglycans and is a candidate for use as an artificial matrix. We developed a novel alginate gel sheet that is crosslinked with heparin (H/A gel sheet) and discovered its properties of releasing biologically active basic fibroblast growth factor (bFGF), a representative member of the heparin-binding growth factors (HBGFs), for about 1 month in vitro and of inducing angiogenesis in vivo. In the present study, the H/A gel sheet was mechanically broken up to produce easily injectable 50- to 200-mum microparticles of the gel (H/A gel particles), the properties of which were analyzed. The H/A gel particles cumulatively released 2.8 times as much bFGF as the H/A gel sheet, despite both having the same amount of bFGF adsorbed onto their gels. In addition, the bFGF-adsorbed H/A gel particles released a significant amount of bFGF, which stimulated cellular growth in a culture of human umbilical venous endothelial cells for up to 5 weeks. The subcutaneous injection of the bFGF-adsorbed H/A gel particles induced the formation of numerous microvessels in the tissue surrounding the gel. These results indicate that the H/A gel particles not only stabilize bFGF by preventing the occurrence of proteolysis or denaturation but also modulate its release from the gel. Because the H/A gel particles can be easily injected into the target tissues, this artificial matrix may be useful for the local delivery of HBGFs in the treatment of ischemic arterial diseases, as well as for regenerating or constructing tissues. (C) 2003 Wiley Periodicals, Inc.